Lipid-dependent regulation of human Th17 cell function
人类 Th17 细胞功能的脂质依赖性调节
基本信息
- 批准号:9176733
- 负责人:
- 金额:$ 44.27万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2016
- 资助国家:美国
- 起止时间:2016-08-01 至 2021-07-31
- 项目状态:已结题
- 来源:
- 关键词:Adverse effectsArthritisAutoimmune DiseasesAutoimmune ProcessBiogenesisCD4 Positive T LymphocytesCell Differentiation processCell LineageCell physiologyCellsChemicalsColitisCytoplasmDataDevelopmentDiseaseDisease modelEffector CellFamilyFatty AcidsFatty LiverGene ExpressionGene TargetingGenesGenetic ScreeningGenetic screening methodGoalsHelper-Inducer T-LymphocyteHumanImmuneInflammationInflammatoryInflammatory Bowel DiseasesInterleukin-17KineticsLeadLigandsLightLinkLipidsLiver diseasesMemoryMetabolicMetabolismModelingMolecularMultiple SclerosisMusNonesterified Fatty AcidsNuclear Hormone ReceptorsOrganellesOrphanPPAR gammaPathologyPathway interactionsPhysiologicalPlayPolyunsaturated Fatty AcidsProductionProteinsPsoriasisRegulationRegulatory T-LymphocyteRetinoidsRoleSpecificitySterolsT cell differentiationT-LymphocyteTestingTriglyceridesabstractingchemical geneticscytokinegain of functionknock-downlipid metabolismmacromoleculenovelnovel therapeuticsprogramsreceptorresponsesmall hairpin RNAsmall moleculetreatment strategy
项目摘要
Abstract
Th17 cells are an Interleukin-17-producing subset of CD4+ T effector cells that are centrally
implicated in many human inflammatory and autoimmune diseases, from inflammatory bowel
disease to multiple sclerosis. The retinoid orphan receptor gamma t (RORγt), a nuclear hormone
receptor, programs Th17 cell development and function. With the ultimate goal of modulating
inflammatory T cells in disease settings, we undertook chemical and genetic screening to
identify RORγt target genes that drive human Th17 cell function. Intriguingly, our results
implicated a group of genes in a novel pathway that would link lipid metabolism, RORγt activity
and Th17 cell functions. We will thus test the hypothesis that Th17 cell function is controlled in
large part, by RORγt target genes, via lipid droplets (LDs) (cellular organelles associated with
lipid metabolism). We will take the following approaches: First, we will determine if LD- related
genes – specifically, HILPDA and BNIP3 – are necessary, sufficient and specific regulators of
human Th17 cell functions. Second, we will elucidate the molecular mechanisms by which LDs
modulate Th17 cell differentiation. Third, using autoimmune disease models in mice, we will
determine the physiological significance of LDs in inflammation and autoimmune pathologies.
Our results may shed a light on novel lipid-regulatory mechanisms that control Th17 cell
responses in inflammatory diseases.
摘要
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Jun R. Huh其他文献
Brain-wide mapping of immune receptors uncovers a neuromodulatory role of IL-17E and the receptor IL-17RB
大脑范围内免疫受体的图谱揭示了 IL-17E 及其受体 IL-17RB 的神经调节作用
- DOI:
10.1016/j.cell.2025.03.006 - 发表时间:
2025-04-17 - 期刊:
- 影响因子:42.500
- 作者:
Yunjin Lee;Tomoe Ishikawa;Hyeseung Lee;Byeongjun Lee;Changhyeon Ryu;Irene Davila Mejia;Minjin Kim;Guangqing Lu;Yujin Hong;Mengyang Feng;Hyeyoon Shin;Sylvain Meloche;Richard M. Locksley;Ekaterina Koltsova;Sergei I. Grivennikov;Myriam Heiman;Gloria B. Choi;Jun R. Huh - 通讯作者:
Jun R. Huh
Apoptosis: Sculpture of a fly's head
细胞凋亡:苍蝇头部雕塑
- DOI:
10.1038/418926a - 发表时间:
2002 - 期刊:
- 影响因子:64.8
- 作者:
Jun R. Huh;B. Hay - 通讯作者:
B. Hay
Maternal gut bacteria drive intestinal inflammation in offspring with neurodevelopmental disorders by altering the chromatin landscape of CD4sup+/sup T cells
母体肠道细菌通过改变 CD4+T 细胞的染色质景观,在患有神经发育障碍的后代中驱动肠道炎症。
- DOI:
10.1016/j.immuni.2021.11.005 - 发表时间:
2022-01-11 - 期刊:
- 影响因子:26.300
- 作者:
Eunha Kim;Donggi Paik;Ricardo N. Ramirez;Delaney G. Biggs;Youngjun Park;Ho-Keun Kwon;Gloria B. Choi;Jun R. Huh - 通讯作者:
Jun R. Huh
Gut-innervating nociceptor neurons protect against enteric infection by modulating the microbiota and Peyer’s patch microfold cells
肠道神经伤害感受器神经元通过调节微生物群和派尔氏集结微褶皱细胞来防止肠道感染
- DOI:
10.1101/580555 - 发表时间:
2019 - 期刊:
- 影响因子:0
- 作者:
N. Lai;Melissa A. Musser;Felipe A. Pinho;P. Baral;Pingchuan Ma;D. Potts;Zuojia Chen;Donggi Paik;Salima Soualhi;Hailian Shi;Aditya Misra;Kaitlin Goldstein;K. Sivanathan;A. Jacobson;Antonia Wallrapp;Valentina N. Lagomarsino;V. Kuchroo;Roni Nowarski;M. Starnbach;N. Surana;Dingding An;Chuan Wu;Jun R. Huh;M. Rao;I. Chiu - 通讯作者:
I. Chiu
Inflammatory and anti-inflammatory cytokines bidirectionally modulate amygdala circuits regulating anxiety
炎症细胞因子和抗炎细胞因子双向调节调节焦虑的杏仁核回路
- DOI:
10.1016/j.cell.2025.03.005 - 发表时间:
2025-04-17 - 期刊:
- 影响因子:42.500
- 作者:
Byeongjun Lee;Jeong-Tae Kwon;Yire Jeong;Hannah Caris;Dongsun Oh;Mengyang Feng;Irene Davila Mejia;Xiaoying Zhang;Tomoe Ishikawa;Brianna R. Watson;Jeffrey R. Moffitt;Kwanghun Chung;Jun R. Huh;Gloria B. Choi - 通讯作者:
Gloria B. Choi
Jun R. Huh的其他文献
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{{ truncateString('Jun R. Huh', 18)}}的其他基金
Dissecting the modulatory functions of interleukin-17 in Alzheimer's Disease
剖析 IL-17 在阿尔茨海默病中的调节功能
- 批准号:
10590495 - 财政年份:2022
- 资助金额:
$ 44.27万 - 项目类别:
Pregnancy influences maternal immune cell function and fetal brain development
怀孕影响母体免疫细胞功能和胎儿大脑发育
- 批准号:
10669604 - 财政年份:2019
- 资助金额:
$ 44.27万 - 项目类别:
Pregnancy influences maternal immune cell function and fetal brain development
怀孕影响母体免疫细胞功能和胎儿大脑发育
- 批准号:
10011840 - 财政年份:2019
- 资助金额:
$ 44.27万 - 项目类别:
Pregnancy influences maternal immune cell function and fetal brain development
怀孕影响母体免疫细胞功能和胎儿大脑发育
- 批准号:
10437718 - 财政年份:2019
- 资助金额:
$ 44.27万 - 项目类别:
Pregnancy influences maternal immune cell function and fetal brain development
怀孕影响母体免疫细胞功能和胎儿大脑发育
- 批准号:
10215459 - 财政年份:2019
- 资助金额:
$ 44.27万 - 项目类别:
Bacterial metabolites controlling Th17 cells
控制 Th17 细胞的细菌代谢物
- 批准号:
9571441 - 财政年份:2016
- 资助金额:
$ 44.27万 - 项目类别:
Lipid-dependent regulation of human Th17 cell function
人类 Th17 细胞功能的脂质依赖性调节
- 批准号:
9316588 - 财政年份:2016
- 资助金额:
$ 44.27万 - 项目类别:
Lipid-dependent regulation of human Th17 cell function
人类 Th17 细胞功能的脂质依赖性调节
- 批准号:
9582212 - 财政年份:2016
- 资助金额:
$ 44.27万 - 项目类别:
Bacterial metabolites controlling Th17 and Treg cells
控制 Th17 和 Treg 细胞的细菌代谢物
- 批准号:
10670406 - 财政年份:2016
- 资助金额:
$ 44.27万 - 项目类别:
Bacterial metabolites controlling Th17 and Treg cells
控制 Th17 和 Treg 细胞的细菌代谢物
- 批准号:
10365478 - 财政年份:2016
- 资助金额:
$ 44.27万 - 项目类别:
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